Glypican-3 mRNA expression level in Wilms tumor: correlation with histological type,stage, and outcome

Purpose

To correlate expression of Glypican-3 in Wilms tumor with histopathology, stage, and outcome.

Methods

Glypican-3 mRNA expression by real-time PCR on tumor and normal germline samples from 75 fresh nephrectomies for Wilms tumor with fold change after normalization against GAPDH was compared. Survival analysis for event-free and overall survival (EFS, OS) with 2-year follow-up for Glypican-3 overexpression (>1.5 times) and clinicopathological parameters was performed.

Results

Glypican-3 was overexpressed in 37/75 (49.3%). It was overexpressed in 77% (10/13) cases with blastema predominance or anaplastic histology, as compared to 44% of other histologies (27/62) (p = 0.03). OS was 73 and 93%, respectively (p = 0.016), for those with and without GPC-3 overexpression. EFS was not significantly different with Glypican-3 overexpression (p = 0.11). All 5 deaths among blastema predominant tumors and 4/5 deaths among triphasic tumors had overexpressed Glypican-3. Most deaths in Stage IV, Stage III, and Stage I + II (5/7, 3/3, 1/1) had GPC-3 overexpression. On multivariate analysis, only histology and stage were found to have independent prognostic value.

Conclusion

Glypican-3 overexpression in Wilms tumor correlates with poor OS on univariate analysis. However, only histology and stage have independent prognostic value. Glypican-3 levels may help to stratify intermediate outcome histology (triphasic) and Stage III Wilms tumors.

     

Biochemical and histopathological evaluation of histamine receptors (H1R,H2R,H3R and H4R)-agonist in rabbits

The present study was designed to investigate the biochemical and histopathological changes in the livers of rabbits treated with histamine and histamine receptors (H1R–H4R)-agonist. The cohort comprised of six groups containing five rabbits each. Control group received sterile distilled water (1 mL/kg × b.i.d.) and treated groups received subcutaneous histamine (100 μg/kg × b.i.d.) and H1R–H4R-agonist (histamine trifluoro-methyl toluidide, amthamine, R-[?]-α-methylhistamine, clobenpropit, respectively) each in a dose of 10 μg/kg × b.i.d. (12 h [8 am and 8 pm]) for 30 days. Hepatotoxicity due to these agonists was analyzed using biochemical and histopathological methods. Histamine and H1R–H3R-agonist were found to be hepatotoxic as shown by statistically significant (p < 0.05) elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), most marked in the H3R-agonist group. However, their levels in H4R-agonist group remained very similar to the control group. The entire drug treated groups as compared to control showed significant elevated levels of alkaline phosphatase (ALP). Histopathological examination revealed obvious changes in histamine, H2R- and H3R-agonist groups in terms of alteration of hepatic microstructure, congestion, focal necrosis and increased incidence of multinucleate hepatocytes while H1R and H4R groups showed minimal changes. From the findings of the present study it may be concluded that on repeated administration, histamine and HR-agonists-induced hepatotoxicity which is most pronounced with H3R-agonist though not severe enough to jeopardize the vital functions of liver and warrants further long-term studies.     

Procedural sedation in children with autism spectrum disorders in the emergency department

Background and objectivesChildren with autism spectrum disorder (ASD) present more frequently to the emergency department (ED) than children with normal development, and frequently have injuries requiring procedural sedation. Our objective was to describe sedation practice and outcomes in children with ASD in the ED.MethodsWe performed a retrospective chart review of children with ASD who underwent sedation at two tertiary care EDs between January 2009–December 2016. Data were collected on children 1–18 years of age with ASD who were sedated in the ED.ResultsThere were 6020 ED visits by children with ASD, 126 (2.1%) of whom received sedation. The most frequent indications for sedation were laceration repair (24.6%), incision and drainage (17.5%), diagnostic imaging (14.3%), and physical examination (11.9%). The most common sedatives used were ketamine (50.8%) and midazolam (50.8%). Ketamine was most commonly given intravenously (71.9%), while midazolam was usually given intranasally (71.9%). Procedures could not be completed in 4 (3.2%) patients, and adverse events were noted in 23 (18.3%) patients. Only four (3.2%) patients required supplemental oxygenation, and one received positive pressure ventilation.ConclusionsChildren with autism in the ED commonly received sedation; one in four of which were for non-painful diagnostic procedures or physical examination. Over one-third received sedation via a non-parenteral route for intended minimal sedation. Sedative medication dosing and observed adverse events were similar to those reported previously in children without ASD. Emergency providers must be prepared to meet the unique sedation needs of children with ASD.     

Physical activity and sedentary behaviours of South Asian and white European children in inner city secondary schools in the UK

BACKGROUND: People of South Asian (SA) origin have an increased risk of premature coronary heart disease. In children of SA origin, there is an increased prevalence of obesity and evidence of insulin resistance. Risk factors for cardiovascular disease in children often persist into adulthood. Low levels of physical activity are likely to be linked to the rise in obesity. OBJECTIVE: To determine levels of physical activity and sedentary behaviours in secondary school pupils in the UK, including comparison of SA and white European (WE) children and those with and without a family history of cardiovascular disease. METHOD: Questionnaire survey conducted within an action research study in five inner city secondary schools serving a predominantly SA population. RESULTS: We obtained 3601 responses from 76% of eligible pupils. WE pupils were more likely to have walked to and from school compared to SAs. However, overall we identified low levels of physical activity and higher levels of inactive behaviours in both ethnic groups. Almost half (46%) of respondents spent four or more hours per day watching television or videos or playing computer games. An overall low level of active behaviour during school breaks was particularly emphasized in girls. We found no evidence of an association between physical activity levels and family history of cardiovascular disease. CONCLUSIONS: There is an urgent need for those with responsibility for young people's health, including parents, schools and community health providers, to consider and address the need for effective interventions to encourage increased physical activity levels.